Diabetes 9,10 Flashcards
Where does energy come from
Carbohydrates, lipids and proteins.
Stored in the body by glycogen and triglycerides
Glycogenesis = conversion of glucose to glycogen, occurs in liver and muscle
Glycogenolysis = conversion of glycogen to glucose
Gluconeogenesis = synthesising glucose from non-carbohydrate sources
Fuel metabolism and blood sugar control
KEy players in fuel metabolism are: Liver, pancreas , muscle and adipose tissue
Blood sugar control is important as:
Carbohydrate is the main source of energy and brains only source of fuel, need effectie mechanism for breaking down carbohydrate etc. Carbohydrates broken down into glucose, blood lvels of glucose mustbe kept within strict limits
What are the symptoms and consequences of hyperglycemia?
Polyuria Thirst Weight loss Fatigue
Neuropathy Nephropathy Heart disease Cataracts and blindness Diabetic coma Death
What are the symptoms and consequences of hypoglycemia?
Irritability and fatigue Food cravings Headaches Dizziness Shaking Confusion
Loss of consciousness Accidents amd injury Weight gain Reduced IQ Brain abnormalities
Anatomy of blood glucose control. Insulin synthesis
Islets of langerhans = alpha cells make glucagon, beta cells make insulin, delta cells make somatostain
Insulin = polypeptide which allows circulating glucose to be used by cells.
In ER, preproinsulin is made. Proinsulin is made by chopping off signal peptide, then paakced into veicles to move to golig apparatus. Production of disulphide bridges occur between alpha and beta chain. Once reache goldi, vesicles form with endopeptides which remove C chain, forming mature insulin/
Glucose sensing and insulin secretion
Gluvose once nside the cell by GLUT2 is phosphorylated using glucokinase into glucose-6-phosphate so it cant move back out the cell.
glucose-6-phosphate enters into cycle where energy is genarated, producing ATP.
When too much ATP is made, K+ channels close, causing depolaraition.
Depolarisation allows Ca channels to open so Ca comes into cell so insulin can be released from vesicles
Describe insulin signalling
Insulin/IGF-1 Receptor tyrosine kinase Recruits the IRS family of proteins Activate Ras, Mek, Erk for general gene expression Activates PI3K, AKT pathway to increase glucose transporter insertion in the membrane AKT and PKC pathways increase glucose metabolism by increasing GLUT4 transposrters into the membrane.
When insulin binds to GLUT4, a number of singlaling pathways are activated
What are the metabolic effects of insulin?
Increase glucose uptake and conversion to glycogen and triglyceride, glycolysis, increase amino acid uptake and protein synthesis
Describe insulin and glucagon
Insulin secreted by the beta cells in the islets of Langerhans Promotes secretion of glycogen and lowers blood sugar
Glucagon has an antagonistic action to insulin, secreted by the alpha cells Secreted in response to low blood sugar and low insulin levels
Glucagon synthesis = peptide hormone in which the polypeptide is borken down in pancreas to active glucagon
Describe the actions of glucagon on the cell
Glucagon reacts with G protein coupled recpetor➡ cAMP➡ PKA = Increases pyruvate and glycogen conversion to glucose
Promotes gluconeogenesis, glycogenolysis, ketogenesis - formation of ketone bodies, lipolysis
Inhibits lipogenesis
Glucagon does the opposite of insulin
Describe some of the other hormones involved in glucose homeostasis
Glucagon-like peptide 1 (GLP1)- produced in response to eating food. Talks to brain to let you know when your full. alternative proteolytic processing in intestinal L cells (not alpha cells) of proglucagon. GLP1 is broken down once no more food in stomach.
Adrenaline Glucocortcoids Somatostatin Growth hormone
Sodium glucose co trasnporters 2 inhibitors allow excess glucose to end up in urine so diabetic pateitns can maintain blood glucose levels.
Insulin resistnace increases as you get fatter, so more insulin is needed to get same effect
Describe type 1 diabetes mellitus
5-10% of cases Beta cells selectively destroyed
Complete lack of insulin
Childhood onset
Genetic component HLA genes are major risk factors
Environmental trigger unknown: causes beta cell lysis and T cell mediated autoimmune response Viral infections, parental age, stress Acute presentation with keto acidosis
Describe type 2 diabetes mellitus
85-95% of cases
Insulin resistance amd beta cell failure
Strongly associated with obesity
Residual insulin so ketosis is rare
Often present with diabetic complication
Part of the metabolic syndrome- diabetes, obesity, hypertension, hyperlipidaemia
Insulin resistance- liver, skeletal muscle fat, reduced uptake of glucose from blood leads to dyslipidaemia and platelet aggregation
Impaired insulin secretion- initial increase to offset resistance followed by progressive deterioration Substantial genetic component
Describe diabetes diagnosis
Fasting plasma glucose >/= 7mmol/l
Oral glucose tolerance test >/= 11.1mmol/l
What are the complications of diabetes?
Hypoglycemia Ketoacidosis- build up of ketone bodies in blood lowers pH
Micro vascular complications- retinopathy- areas of hypoxia in retina leads to progressive blindness, nephropathy- protein urea, neuropathy- degenerative disorders of peripheral nerves can lead to ulcers, gangrene and amputation
Macrovascular- due to lipid disorders promotes atherosclerosis
